Delivery of Insulin via Skin Route for the Management of Diabetes Mellitus: Approaches for Breaching the Obstacles

Abstract

Insulin is used for the treatment of diabetes mellitus, which is characterized by hyperglycemia. Subcutaneous injections are the standard mode of delivery for insulin therapy; however, this procedure is very often invasive, which hinders patient compliance, particularly for individuals requiring insulin doses four times a day. Furthermore, cases have been reported of sudden hypoglycemia occurrences following multidose insulin injections. Such an invasive and intensive approach motivates the quest for alternative, more user-friendly insulin administration approaches. For example, transdermal delivery has numerous advantages, such as prolonged drug release, low variability in the drug plasma level, and improved patient compliance. In this paper, the authors summarize different approaches used in transdermal insulin delivery, including microneedles, chemical permeation enhancers, sonophoresis, patches, electroporation, iontophoresis, vesicular formulations, microemulsions, nanoparticles, and microdermabrasion. Transdermal systems for insulin delivery are still being widely researched. The conclusions presented in this paper are extracted from the literature, notably, that the transdermal route could effectively and reliably deliver insulin into the circulatory system. Consistent progress in this area will ensure that some of the aforementioned transdermal insulin delivery systems will be introduced in clinical practice and commercially available in the near future.

Transdermal permeation of curcumin promoted by choline geranate ionic liquid: Potential for the treatment of skin diseases

“…Porcine ear skin has been often used as a mimicking alternative to the human skin in studies of percutaneous absorption when developing formulations for transdermal delivery of bioactive moieties ( Boscariol et al, 2021 , Silva et al, 2021 , Hernandes et al, 2021 , Jorge et al, 2020 , Campos et al, 2020 , Todo, 2017 , Zakrewsky et al, 2016 ). Several in vitro studies of transdermal permeation using Franz cells have indicated that porcine ear skin is the one that has flow values and permeation coefficients closest to the human skin ( Ahad et al, 2021 , Islam et al, 2020 ).…”

Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases

“…Alternative delivery methods attempted: implantable device, needle-free jet injection, transdermal delivery, microneedle-based delivery, pulmonary delivery [21][22][23][24][25]. There has been a shift in reliance, from synthetic human insulin towards insulin analogues.…”

“…Alternative routes of peptide delivery have been developed and tested. Throughout the years, various new methods have been employed to increase the ease of the delivery of insulin, such as the use of an implantable device [ 21 ], needle-free jet injection [ 22 ], and microneedle-based transdermal delivery [ 23 , 24 ]. Pulmonary delivery of inhalable insulin has been considered as an attractive delivery method, however, it has raised safety concerns with side effects resulting in commercial failures [ 25 ].…”

Charting the next century of insulin replacement with cell and gene therapies

“…We recommend readers to the two recent reviews describing the different strategies and formulations of transdermal insulin delivery. 62,63 Of these, several versions of jet injectors have completed the final phases in clinical trials, and products including Vitajet 3, InsuJet, Injex, and Comfort-In Needle Free Injectors are available on the market for individuals living with diabetes. Insulin is loaded into a cartridge via adaptors from insulin pens or vials and connected to spring-loaded devices.…”